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PubMed2006

Mycosis fungoides associated with B-cell malignancies.

BACKGROUND: The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. OBJECTIVES: To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. METHODS: Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. RESULTS: Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. CONCLUSIONS: This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Adult↗
PubMed2006

Decreased CD117 expression in hypopigmented mycosis fungoides correlates with hypomelanosis: lessons learned from vitiligo.

Hypopigmented mycosis fungoides is an uncommon clinical variant of cutaneous T-cell lymphoma. We hypothesized that hypomelanosis in hypopigmented mycosis fungoides may have a similar mechanism as in vitiligo, a condition in which it is believed that alterations in expression of CD117 (stem cell factor receptor/KIT protein) on epidermal melanocytes and abnormal interactions between melanocytes and surrounding keratinocytes may play a pathogenic role. To test the hypothesis that similar mechanisms might also explain hypopigmentation in hypopigmented mycosis fungoides, skin specimens from five cases each of hypopigmented mycosis fungoides and vitiligo were studied immunohistochemically for immunophenotype of the infiltrating cells, CD117 (expressed by epidermal melanocytes), and pan melanoma cocktail of antigens (gp100, tyrosinase, and MART-1) expression; cases of conventional mycosis fungoides and normal skin were studied in parallel as controls. Our findings confirm a predominance of CD8+ neoplastic T cells in hypopigmented mycosis fungoides. Similarly, the epidermal lymphocytic infiltrate in vitiligo was also composed of CD8+ cytotoxic T cells, in contrast to an epidermal infiltrate composed of CD4+ T cells in conventional mycosis fungoides. The average number of epidermal CD117 expressing cells followed the same pattern of decreased expression in hypopigmented mycosis fungoides as in vitiligo, whereas the levels in conventional mycosis fungoides were higher, and similar to that observed in normal skin. Furthermore, a decreased number of melanocytes per high-power field of the length of the biopsy was present in hypopigmented mycosis fungoides and vitiligo, as compared with either conventional mycosis fungoides or normal skin, suggesting a correlation between decreased expression of CD117 and decreased number of melanocytes. We propose that decreased expression of CD117 and its downstream events in melanocytes may be initiated by cytotoxic effects of melanosomal-antigen-specific CD8+ neoplastic T lymphocytes, resulting in destabilization of CD117 and leading to dysfunction and/or loss of melanocytes in the epidermis of hypopigmented mycosis fungoides.

Antigens, Neoplasm↗
PubMed1987

Light microscopic, S-100 immunostaining, and ultrastructural analysis of dermatopathic lymphadenopathy, with and without associated mycosis fungoides.

Thirty-five patients with dermatopathic lymphadenopathy, 12 with (9 patients and 3 follow-up) and 23 without associated mycosis fungoides, and 7 controls with 26 lymph nodes were studied by light microscopic examination and immunostaining for S-100 protein. Fourteen of these cases were examined ultrastructurally. The group of cases studied included lymph nodes obtained at postmortem examination from three patients with mycosis fungoides and evidence of nodal involvement by light microscopic examination. Lymph nodes from patients with dermatopathic lymphadenopathy and paracortical hyperplasia (but no effacement of architecture by recognizable mycosis fungoides cells by light microscopic examination) associated with biopsy-proven mycosis fungoides showed well-defined, diffusely distributed sheets of S-100-positive cells. Cases of dermatopathic lymphadenopathy unassociated with a skin lymphoma (23 cases), with the exception of 3 cases (12.5%), only showed scattered S-100-positive cells, a similar pattern to that noted in normal or reactive lymph nodes from the control cases and reported literature. In the three cases with diffuse sheets without associated mycosis fungoides, the intensity of S-100 staining was the same in germinal centers as in parafollicular areas, while in cases associated with mycosis fungoides, the staining was predominantly in parafollicular zones. Ultrastructural immunolabeling for S-100 protein also revealed different patterns in both subsets of patients. Interestingly, in cases in which the lymph nodes were identified by light microscopic examination to be replaced by mycosis fungoides, the sheets of S-100-positive cells disappeared. The corresponding ultrastructural evaluation showed cellular aggregates with features of T-cells. A combination of S-100 immunocytochemistry and morphologic ultrastructural assessment can be of help in evaluation of lymphadenopathy in patients with mycosis fungoides. Although this study indicates that the finding of sheets of S-100-positive cells in patients with dermatopathic lymphadenopathy is not always associated with mycosis fungoides, the identification of diffuse sheets of S-100-positive cells, especially with parafollicular distribution, in a patient without known T-cell lymphoma should probably be considered an indication to suggest a complete clinical evaluation to rule out the possibility of an undiagnosed mycosis fungoides. The finding of sheets of S-100-positive cells in patients with proven mycosis fungoides may be a morphologic indicator of impending extracutaneous dissemination.

Dermatitis↗
PubMed1990

Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease.

Skin biopsies from seven patients with mycosis fungoides in various clinical stages (patches, plaques, nodules) were studied immunohistochemically and ultrastructurally, with the aim of investigating and quantifying the distribution of Langerhans cells and their relationships to mycosis cells. Our findings have revealed that in patches and plaques both Langerhans cells and mycosis cells were numerous in the epidermis. Notwithstanding this, in all the specimens examined, only one Langerhans cell forming close contact with a mycosis cell was detected. In the nodules, Langerhans cells and mycosis cells were sparse in the epidermis and no contacts were seen between them. Moreover, in all the patients studied, only a single Langerhans cell was found in the dermal infiltrate without any closely related mycosis cells. Conversely, numerous interdigitating cells have been found in the dermis of patches and plaques, often tightly adhering to mycosis cells. In the nodule, a few scattered interdigitating cells were seen, but often these had close contacts with neoplastic lymphoid cells. These findings indicate that close apposition between Langerhans cells and mycosis cells, which led previous authors to hypothesize a persistent stimulatory action of Langerhans cells on T lymphocytes, eventually leading to the malignant transformation of the latter, is unusual in mycosis fungoides. Therefore, if such a pathogenic role may be attributed to accessory cells in mycosis fungoides it is more probably exerted by dermal interdigitating cells and not by Langerhans cells, as previously proposed.

Humans↗
PubMed2001

Reassessment of lymphocytic atypia in the diagnosis of mycosis fungoides.

The manifestations of mycosis fungoides in its early stage may mimic clinically and histologically those of many benign inflammatory dermatoses. Therefore, the diagnosis of mycosis fungoides remains a major challenge for dermatologists and dermatopathologists. For many years, it has been proposed that atypical lymphocytes within the epidermis constitute one of the diagnostic features in mycosis fungoides. Presence of dermal atypical lymphocytes remains controversial as a diagnostic criterion. We reassessed the feasibility of applying lymphocytic atypia within epidermis and dermis as diagnostic criteria discriminating between mycosis fungoides and spongiotic dermatitis. Thirty cases of mycosis fungoides and 30 cases of spongiotic dermatitis were retrieved from archival hematoxylin and eosin-stained histologic sections. Punch biopsy sections were examined by light microscopy; epidermal and dermal lymphocytes were photographed at 1000x (oil immersion). A total of 92 ektachrome slides (35 mM) were developed, coded, and ordered randomly. For each slide, cells were interpreted as typical or atypical lymphocytes by seven pathologists. Atypical epidermal lymphocytes were judged to be present in 9 +/- 2 out of 16 (56%) cases of mycosis fungoides photographed as compared with 8 +/- 3 out of 16 (50%) in spongiotic dermatitis. Dermal lymphocytic atypia was thought to be present in 14 +/- 6 out of 30 (47%) patients with mycosis fungoides. Thirteen +/- 6 out of 30 (43%) patients with non-mycosis fungoides also displayed dermal lymphocytic atypia. No statistical significance was observed in these comparisons (t test, P >.05). Furthermore, atypia of lymphocytes was deemed to be present in 41, 38, 59, 70, 23, 47, and 40 out of 92 slides examined by the investigators, suggesting that observer variation is a very significant factor in our present study. We conclude that it is not possible to distinguish mycosis fungoides from spongiotic dermatitis merely based on lymphocytic atypia within epidermis or dermis.

Dermatitis↗
PubMed1988

Granulomatous variants of cutaneous T-cell lymphoma. The histopathology of granulomatous mycosis fungoides and granulomatous slack skin.

Granulomatous mycosis fungoides is an unusual histologic variant of mycosis fungoides, a condition that is ordinarily indolent. Granulomatous slack skin, like granulomatous mycosis fungoides, shows epidermotropism, granulomatous inflammation, a clonal T-helper cell population, and progression to systemic lymphoma in some cases. Unlike granulomatous mycosis fungoides, it is characterized clinically by bulky, pendulous skin folds. The similarities between the two conditions prompted us to compare the histologic features. We reviewed 24 biopsies from 10 patients with granulomatous mycosis fungoides. These showed several distinct histologic patterns, including three cases that mimicked granuloma annulare. We also reviewed biopsy specimens from four patients with granulomatous slack skin. These specimens had a more stereotypic appearance, with permeation of the entire dermis and subcutis by lymphocytes, marked epidermotropism, and a more even distribution of granulomas and giant cells within the infiltrate. Biopsies of fully developed lesions of granulomatous slack skin showed elastolysis involving the full thickness of the dermis--a feature not seen in any of our granulomatous mycosis fungoides cases. Biopsy specimens from granulomatous mycosis fungoides and granulomatous slack skin may be mistaken for nonneoplastic granulomatous dermatitides, but they can usually be distinguished from these by the presence of epidermotropism or atypical lymphocytes. Because several of our patients with granulomatous mycosis fungoides died after courses of unremarkable length, it seems unlikely that the presence of granulomas is invariably correlated with a more benign course than nongranulomatous mycosis fungoides.

Adolescent↗
PubMed2003

Carbamazepine-induced pseudo mycosis fungoides.

OBJECTIVE: To report a case of pseudo mycosis fungoides due to carbamazepine. CASE SUMMARY: A 54-year-old man experienced a skin lesion resembling mycosis fungoides without any systemic symptoms or signs 2 months after he had begun carbamazepine treatment for his seizures. Skin-punch biopsy specimens revealed mycosis fungoides-like histopathologic appearance. After drug discontinuation, the patient experienced complete remission of the clinical and pathologic findings. This suggests a diagnosis of pseudo mycosis fungoides due to carbamazepine. DISCUSSION: Mycosis fungoides is the cutaneous T-cell lymphoma of the skin that needs aggressive chemotherapy and radiation treatment. Pseudo mycosis fungoides is a condition caused by certain drugs that has a similar clinical and histopathologic appearance to mycosis fungoides. When the causative drug is discontinued, the lesions resolve completely. CONCLUSIONS: An objective causality assessment revealed that carbamazepine was highly probable as the cause of the adverse reaction. Patients who are diagnosed with mycosis fungoides should be asked about any drug use, and clinicians should recognize signs of pseudo mycosis fungoides.

Carbamazepine↗
PubMed1986

Leu-8 and Leu-9 antigen phenotypes: immunologic criteria for the distinction of mycosis fungoides from cutaneous inflammation.

The distinction of mycosis fungoides from reactive cutaneous inflammation can be difficult. Unfortunately, since many reactive processes exhibit predominantly a mature helper T cell phenotype similar to that expressed by most cases of mycosis fungoides, standard immunologic marker studies have not been very helpful in differential diagnosis. To determine whether novel immunophenotypic criteria could be developed that correlate with the diagnosis of cutaneous involvement by mycosis fungoides, we studied the expression of Leu-8 and Leu-9 antigens by T cells in forty-one skin biopsy specimens from twenty-seven patients with mycosis fungoides and thirty-four skin biopsy specimens from thirty-three controls with a variety of benign cutaneous diseases. These antigens are expressed by the majority of normal T cells in the blood and lymphoid tissues but are often absent in T cell lymphomas or expressed by only a minority of tumor cells. Semiquantitative grading of the percentage of Leu-8+ and Leu-9+ T cells in our patients revealed that deficiency of these antigens (i.e., expression by less than or equal to 33% of T cells) was more prevalent among mycosis fungoides patients than among controls and became more specific for mycosis fungoides as the percentage of Leu-8+ and Leu-9+ T cells decreased. In initial biopsies, less than or equal to 33% of T cells were Leu-8+ in 82% of mycosis fungoides patients versus 15% of controls, while less than or equal to 10% of T cells were Leu-8+ in 52% of mycosis fungoides patients versus only 3% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, T-Lymphocyte↗
PubMed2003

Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides.

We analyzed the expression of 13 chemokine receptors in mycosis fungoides, in order to assess the contribution of chemotaxis to the pathogenesis of the disease. Material from skin biopsies of six patients with early disease and six patients at the tumor stage of mycosis fungoides was analyzed by immunohistochemistry and partly also by flow cytometry. The receptors CCR1, CCR2, CCR3, CCR5, CCR6, CXCR1, CXCR2, CXCR5, and CX3CR1 were rarely and inconsistently detected in lesional skin and thus their participation in mycosis fungoides could largely be ruled out. In contrast, CCR4, CXCR3, and CXCR4 were substantially expressed on both mycosis fungoides cells and the surrounding reactive T cells in the early patch and plaque stages of the disease, indicating an involvement of these chemokine receptors in the disease process. In the tumor stage of mycosis fungoides, we interestingly observed a loss of a relevant chemokine receptor in four out of six patients. In three patients CXCR3 and in one patient CCR4 was absent on tumor mycosis fungoides cells, whereas the reactive T cells showed normal levels of expression. Within these samples, tumor mycosis fungoides cells exhibited high levels of CCR7, a chemokine receptor central for the entry of T cells to lymphatic tissue. Taken together, our data suggest that the loss of one or more of the chemokine receptors involved in the homing of the mycosis fungoides cells to the skin may trigger the latent potential of these cells to metastasize into regional lymphatic tissue.

Adult↗
PubMed2000

Rapidly progressing mycosis fungoides presenting as follicular mucinosis.

Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides. We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides. In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides.

Adult↗
PubMed1991

Thy-1 and T-cell receptor antigen expression in mycosis fungoides and benign inflammatory dermatoses.

We have studied human Thy-1 and T-cell receptor (TCR) antigen expression in mycosis fungoides and benign inflammatory dermatoses. The study included 24 biopsy specimens from 21 patients with mycosis fungoides (nine patch stage from eight patients, 13 plaque stage from 11 patients, and two tumor stage from two patients), six specimens from five patients with premycotic parapsoriasis (pre-mycosis fungoides), three specimens from three patients with lichen planus, 11 specimens from 11 patients with lupus erythematosus, 13 specimens from 13 patients with dermatitis, six specimens from six patients with drug eruptions, nine normal skin specimens from nine subjects, and three specimens from three patients with small plaque (benign) parapsoriasis. Immunoperoxidase studies using the avidin-biotin complex technique on serial frozen sections were performed. Primary antibodies were anti-human Thy-1, anti-alpha heterodimer of the TCR, anti-beta heterodimer of the TCR, and anti-delta heterodimer of the TCR. An extensive dendritic network of Thy-1+ cells was seen in all cases of mycosis fungoides. Epidermotropic cells were Thy-1 negative, and Thy-1 was expressed perivascularly in normal individuals and patients as previously reported. Epidermal gamma/delta cells were seen only in mycosis fungoides, where up to 60% of the epidermal lymphocytes expressed this TCR. The increased numbers of Thy-1 and gamma/delta T cells in mycosis fungoides were statistically significant when compared with normal skin or benign inflammatory dermatoses. The role of these dendritic dermal Thy-1+ cells and epidermal gamma/delta T cells in mycosis fungoides is unclear. The significant numbers of these potentially immunomodulating cells that were seen suggest that they are involved in the pathogenesis of mycosis fungoides.

Antigens, Surface↗
PubMed1986

Dermatopathic lymphadenopathy. An immunophenotypic comparison of cases associated and unassociated with mycosis fungoides.

Documenting focal mycosis fungoides in lymph node biopsies that exhibit dermatopathic lymphadenopathy is morphologically difficult. Since mycosis fungoides is a lymphoma with the phenotype of mature T cells, usually of the T-helper class, the authors investigated whether there are alterations in the ratio of Leu 3a (T-helper):Leu 2a (T-suppressor) cells in dermatopathic lymphadenopathy in order to determine the significance of immunologic markers as a possible solution to the problem. Ten lymph node biopsy specimens with diagnostic evidence of dermatopathic lymphadenopathy, but not of mycosis fungoides, were studied with the use of fresh-frozen section immunohistochemistry (FS), cell suspensions (CS), or both; five of the specimens came from patients with known cutaneous mycosis fungoides, and the other five came from patients without mycosis fungoides. The mean Leu 3a/Leu 2a ratio was 7.0 +/- 1.06 (SE) in all 10 cases of dermatopathic lymphadenopathy studied by FS and 6.9 +/- 1.14 in the 6 cases studied by CS. These ratios were significantly higher (P less than 0.001) than the mean Leu 3a/Leu 2a ratios of 2.9 +/- 0.29 (FS) and 2.4 +/- 0.22 (CS) in control lymph nodes exhibiting nonspecific reactive follicular hyperplasia, but were comparable to the mean Leu 3a/Leu 2a ratio of 5.9 obtained in two lymph node biopsies with unequivocal involvement by mycosis fungoides. Despite the increase in Leu 3a staining cells in dermatopathic lymphadenopathy, however, there were no essential differences in the Leu 3a/Leu 2a ratios between patients with and those without known mycosis fungoides. The use of other antibodies reactive with T cells, such as anti-Leu 8, anti-Leu 9, and anti-Tac also did not aid in this discrimination. The results indicate that determination of the Leu 3a/Leu 2a ratio and use of other conventional T-cell monoclonal antibodies do not provide conclusive evidence in support of a presumptive or early diagnosis of mycosis fungoides in a lymph node which fails to show histologic evidence of the disease.

Animals↗